title: The p59 oligoadenylate synthetase-like protein possesses antiviral activity that requires the C-terminal ubiquitin-like domain.
abstract: Viral infection of mammalian cells prompts the innate immune system to initiate an antiviral response. The recognition of the virus triggers several antiviral signalling pathways, which among others include the family of 2'-5' oligoadenylate synthetase (OAS) proteins. The p59 protein encoded by the OAS-like (OASL) gene is an atypical member of the OAS family in the sense that it lacks the characteristic 2'-5' oligoadenylate synthetase activity. We decided to investigate the putative antiviral activity of p59 by ectopically expressing this protein in Vero cells and then infecting these cells with virus. We demonstrate that OASL has an antiviral effect against the single-stranded RNA virus picornavirus, encephalomyocarditis virus, but not against a large DNA virus, herpes simplex virus 1. Importantly, this antiviral activity was lost in a truncated version of p59 lacking the ubiquitin-like C-terminal domain of p59. Taken together our results indicate that p59 is indeed an antiviral protein that works through a novel mechanism distinct from other OAS proteins.
authors.affiliation: Department of Cancer Biology, The Cleveland Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Joao
authors.initials: J
authors.lastname: Marques
authors.affiliation: Centre for Structural Biology, Department of Molecular Biology, University of Aarhus, Gustav Wieds vej 10 C, 8000 Aarhus C, Denmark.
authors.forename: Jangawar
authors.initials: J
authors.lastname: Anwar
authors.affiliation: Centre for Structural Biology, Department of Molecular Biology, University of Aarhus, Gustav Wieds vej 10 C, 8000 Aarhus C, Denmark.
authors.forename: Signe
authors.initials: S
authors.lastname: Eskildsen-Larsen
authors.affiliation: Department of Cancer Biology, The Cleveland Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Dominique
authors.initials: D
authors.lastname: Rebouillat
authors.affiliation: Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
authors.forename: Soren R
authors.initials: SR
authors.lastname: Paludan
authors.affiliation: Department of Molecular Genetic, The Cleveland Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Ganes
authors.initials: G
authors.lastname: Sen
authors.affiliation: Monash Institute of Medical Research, 246 Clayton Road, Clayton, VIC 3168, Australia.
authors.forename: Bryan R G
authors.initials: BRG
authors.lastname: Williams
authors.affiliation: Centre for Structural Biology, Department of Molecular Biology, University of Aarhus, Gustav Wieds vej 10 C, 8000 Aarhus C, Denmark.
authors.forename: Rune
authors.initials: R
authors.lastname: Hartmann
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000276:immunology / Q000378:metabolism*; D002417:Cattle; D002645:Chickens; D017124:Conserved Sequence; D004285:Dogs; D006736:Horses; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000378:metabolism*; D014777:Virus Diseases / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D025801:Ubiquitin; C115020:OASL protein, human; D015088:2',5'-Oligoadenylate Synthetase